Hematopoiesis is an essential, lifelong process whereby highly specialized blood cells are generated from hematopoietic stem cells, including cells responsible for carbon dioxide and oxygen transport (erythrocytes), blood clotting (platelets), humoral immunity (B lymphocytes), cellular immunity (T lymphocytes), as well as cells which respond to foreign organisms and their products (granulocytes, monocytes, and macrophages). All of these cells can be functionally divided into two distinct groups termed myeloid and lymphoid. During normal human adult life, myeloid cells are produced exclusively within the bone marrow (Lichtman, M. A., Exp.Hematol. 9:391, 1981) while cells of the lymphoid lineage are produced to varying degrees in the bone marrow, spleen, thymus, and lymph nodes. Mature functional end cells and their immediate precursors have a limited life-span and a limited proliferative capacity and hence are not self-maintaining. Thus, these cells are continuously replaced from a pool of more primitive proliferating progenitor cells. Ultimately, all cells of both the myeloid and lymphoid lineage are derived from totipotent stem cells. In the normal human adult it is estimated that approximately 200 billion erythrocytes (Erslev, A. J., Hematology, McGraw-Hill, New York, 1983) and 60 billion neutrophilic leukocytes (Dancey, J. T. et al, J. Clin. Invest. 58:705, 1976) are produced everyday.
Hematopoiesis is necessarily tightly regulated. The molecules responsible for regulating various aspects of hematopoiesis can generally be divided into two groups: extracellular growth factors and intracellular factors (e.g. growth factor receptors, signaling molecules and transcriptional factors). Hematopoietic cytokines have been successfully used to treat various diseases arising from imbalances between degradation and reconstitution of blood cells or from generation of inappropriate numbers of certain blood cells. For example, recombinant erythropoietin (EPO) is a glycoprotein administered for the treatment of anemia in chronic renal failure patients, zidovudine-treated HIV-infected patients, cancer patients on chemotherapy, and patients receiving autologous transfusions. Recombinant thrombopoietin (TPO) is currently undergoing clinical evaluation for treatment of thrombocytopenia. In spite of the availability of EPO and TPO, there remains a need to provide additional methods of altering the hematopoietic state of an individual. Accordingly, it is an object of the present invention to provide novel methods of treatment that can prevent and/or correct an undesired hematopoietic condition in a patient.